Ventricular tachycardia (VT) causes about 400,000 out-of-hospital sudden cardiac deaths each year in the United States. An important therapeutic strategy is to interrupt the arrhythmic circuit by catheter ablation of the culprit tissue. The staus quo of VT ablation is tightly interwoven with a catheter mapping procedure that assembles voltage and/or activation maps point-by-point on the heart surface. This mapping procedure is invasive, time-consuming, lacking complete 3D data beneath the heart surface, and limited in spatial resolution. With this practice, physicians are engaged in a prolonged clinical procedure to acquire information at only limited sites where the catheter tip is placed. These fundamental limitations have contributed to high recurrence and high complication rates of VT ablation. The long-term goal of the proposed research is to develop a noninvasive transmural electrophysiological imaging (TEPI) system to map ventricular arrhythmia and to provide pre-procedural planning of VT ablation. Based on our strong preliminary data, the overall objective of this proposal is to optimize and determine the clinical value of TEPI in two critical pre-ablatin utilities. First, we will determine the performance of TEPI in electroanatomical scar imaging and in predicting the inducibility of TEPI. Our hypothesis is that, in comparison to invasive electroanatomical voltage mapping, noninvasive TEPI is more consistent with delayed contrast-enhanced imaging in scar delineation and its scar metrics are more predictive of VT inducibility. Second, we will determine the ability of TEPI to map ventricular arrhythmia and to predict ablation targets. Our hypothesis is that TEPI can be used to map ventricular arrhythmia and identify successful ablation sites. These investigations will be carried out in detailed animal models using post-infarction porcine hearts, involving collaborations between an interdisciplinary team of computational, experimental, and clinical scientists. At the completion of this project, we will be able to determine the clinical utility of TEPI in VT ablation, and to generate important pilot data for designing a R01 clinical study with increased statistical power. We will obtain a noninvasive, transmural, and high-resolution imaging tool to characterize both the substrate and dynamics of ventricular arrhythmia, which is expected to improve the clinical outcome of VT ablation by providing better pre-procedural planning and targeting. In the long term, this research will contribute to the fundamental change of clinical electrophysiological studies from being invasive, surface-based, and point-by-point to being noninvasive, transmural, and high-resolution. It will improve the efficacy and safety of electrophysiological study while reducing its duration and cost in routine clinical practice for a broader spectrum of heart rhythm disorders.